Ketogenic diet for super-refractory status epilepticus (SRSE) with NORSE and FIRES: Single tertiary center experience and literature data

Abstract

Background and purposeKetogenic diet (KD) is an emerging treatment option for super-refractory status epilepticus (SRSE). We evaluated the effectiveness of KD in patients presenting SRSE including NORSE (and its subcategory FIRES).MethodsA retrospective review of the medical records was performed at the Necker Enfants Malades Hospital. All children with SRSE in whom KD was started during the last 10 years were included. A systematic search was carried out for all study designs, including at least one patient of any age with SRSE in whom KD was started. The primary outcome was the responder rate and Kaplan–Meier survival curves were generated for the time-to-KD response. As secondary outcomes, Cox proportional hazard models were created to assess the impact of NORSE-related factors on KD efficacy.ResultsSixteen children received KD for treatment of SRSE, and three had NORSE presentation (one infectious etiology, two FIRES). In medical literature, 1,613 records were initially identified, and 75 were selected for review. We selected 276 patients receiving KD during SRSE. The most common etiology of SRSE was acute symptomatic (21.3%), among these patients, 67.7% presented with NORSE of immune and infectious etiologies. Other etiologies were remote symptomatic (6.8%), progressive symptomatic (6.1%), and SE in defined electroclinical syndromes (14.8%), including two patients with genetic etiology and NORSE presentation. The etiology was unknown in 50.7% of the patients presenting with cryptogenic NORSE, of which 102 presented with FIRES. Overall, most patients with NORSE benefit from KD (p < 0.004), but they needed a longer time to achieve RSE resolution after starting KD compared with other non-NORSE SRSE (p = 0.001). The response to KD in the NORSE group with identified etiology compared to the cryptogenic NORSE was significantly higher (p = 0.01), and the time to achieve SE resolution after starting KD was shorter (p = 0.04).ConclusionsThe search for underlying etiology should help to a better-targeted therapy. KD can have good efficacy in NORSE; however, the time to achieve SE resolution seems to be longer in cryptogenic cases. These findings highlight the therapeutic role of KD in NORSE, even though this favorable response needs to be better confirmed in prospective controlled studies.

Outcome of emergency neurosurgery in patients with refractory and super-refractory status epilepticus: a systematic review and individual participant data meta-analysis

“…Thus, patients with unexplained new onset seizures such as new onset refractory status epilepticus (NORSE) with generalized ictal EEG findings and diffuse or normal imaging findings could still benefit from these approaches. However, our logistic regression models revealed that new-onset seizures were associated with worse outcomes; thus, clinical decision-making should still be made on a case-by-case basis given the lack of high-quality evidence guiding therapy in these patients, as well as the documented role of therapies such as the ketogenic diet and immunotherapy ( 31 , 32 ). Some authors suggest the use of non-invasive neuromodulation techniques such as and transcranial magnetic stimulation (TMS) and electroconvulsive therapy (ECT) in the first week of SRSE, and consideration of neuromodulation techniques such as VNS, DBS and RNS after 2 weeks of therapy ( 33 ).…”

Case report: Febrile infection-related epilepsy syndrome in a 14-year-old girl with multiple organ failure and lethal outcome

“…Although we induced KD within 48 h after admission to our PICU and restricted oral and intravenous glucose intake, a katabolic metabolism was never achieved, with ketone levels rising to a maximum of 0.7 mmoL/L. Previous authors described a similar difficulty in establishing katabolic metabolism in adolescent patients (Nabbout et al, 2023). Based on the possible role of neuroinflammation, steroids and IVIG are used in the treatment of FIRES (Kessi et al, 2020).…”